Lenalidomide and Sintilimab for Relapsed/Refractory NK/T-cell Lymphoma

Combination of Lenalidomide and Sintilimab for Patients With Relapsed/Refractory NK/T-cell Lymphoma Who Failed Pegaspargase-based Regimens: a Single Arm, Open, Phase II Study

The purpose of this study is to evaluate the efficacy and safety of Sintilimab in combination with lenalidomide in the treatment of Relapsed/Refractory NK/T-cell lymphoma patients who failed pegaspargase-based regimens.

Study Overview

• Status: Unknown
• Conditions: NK/T Cell Lymphoma Nos
• Intervention / Treatment: Drug: Sintilimab; Drug: Lenalidomide

Detailed Description

Pegaspargase is the backbone of treatment for NK/T-cell lymphoma (ENKTCL), and patients with ENKTCL who failed pegaspargase-based regimens have extremely poor survival outcomes. Previous study has confirmed the efficacy of anti-PD-1 antibodies (including pembrolizumab or sintilimab). Constitutive activation of NF-kB pathway has been demonstrated to be involved in the development of ENKTCL and plays critical role in therapy resistance. Lenalidomide, an immuno-modulatory drug, has been found to inhibit NF-kB pathway, and synergize with anti-PD-1 antibody in the treatment of multiple myeloma. Thus, we hypothesize that the combination of lenalidomide and sintilimab will further deepen the remission status and benefit patients who failed pegaspargase-based regimens.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100730
    • Recruiting
    • Beijing Tongren Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histopathology and immunohistochemistry confirmed diagnosis of NK/T-cell lymphoma according to WHO 2016 criteria.
• Previously treated with pegaspargase-based regimens (refractory or relapsed after initial remission).
• PET/CT or CT/MRI with at least one objectively evaluable lesion.
• General status ECOG score 0-3 points.
• The laboratory test within 1 week before enrollment meets the following conditions:

Blood routine: Hb>80g/L, PLT>50×10（9）/L. Liver function: ALT, AST, TBIL ≤ 2 times the upper limit of normal. Renal function: Cr is normal. Coagulation : plasma fibrinogen ≥ 1.0g / L. Cardiac function: LVEF≥50%, ECG does not suggest any acute myocardial infarction, arrhythmia or atrioventricular conduction above I Blocking.

• Sign the informed consent form.
• Voluntary compliance with research protocols, follow-up plans, laboratory and auxiliary examinations.

Exclusion Criteria:

• Patients with a history of pancreatitis.
• Active infection requires ICU treatment.
• Concomitant HIV infection or active infection with HBV, HCV. Patients who are infected with HBV but not active hepatitis at the same time are not excluded.
• Serious complications such as fulminant DIC.
• Significant organ dysfunction: such as respiratory failure, NYHA classification ≥ 2 chronic congestive heart failure, decompensation Hepatic or renal insufficiency, high blood pressure and diabetes that cannot be controlled despite active treatment, and cerebral vascular thrombosis or hemorrhagic time within the past 6 months.
• Pregnant and lactating women.
• Had a history of autoimmune diseases, and disease was active in the last 6 months, and was still taking oral immunosuppression in the past three months.
• Those who were known to be allergic to drugs in the study regimen.
• Patients with other tumors who require surgery or chemotherapy within 6 months.
• Other experimental drugs are being used.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment arm; Sintilimab, 200mg, iv day1 Lenalidomide, 25mg/d, oral, day 1-14 repeated every 3 weeks	Drug: Sintilimab; Sintilimab, 200mg, iv day1; Other Names: anti-PD-1-antibody; Drug: Lenalidomide; 25mg/d oral d1-14; Other Names: IMids

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of complete response	evaluated by PET-CT and MRI, according to Lugano 2014 criteria	24 weeks ±7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year progression free survival rate	time from date of enrollment to date of disease progression, death of any reason, whichever comes first	up to 1year after enrollment
Rate of overall response	evaluated by PET-CT and MRI, according to Lugano 2014 criteria	24 weeks ±7 days
1-year overall survival rate	time from date of enrollment to date of death of any reason	up to 1year after enrollment
safety profiles	according to CTCAE 4.0	up to 1year after enrollment

Collaborators and Investigators

• Sponsor: Beijing Tongren Hospital
• Investigators: Principal Investigator: Jing-wen Wang, M.D., Beijing Tongren Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2020
• Primary Completion (Anticipated): February 28, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: January 14, 2020
• First Submitted That Met QC Criteria: January 14, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): May 7, 2020
• Last Update Submitted That Met QC Criteria: May 6, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: lenalidomide; PD-1; sintilimab; pegaspargase; relapsed/refractory
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: TRhos-ENKTCL-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All the data in the trial can be shared upon request to the PI.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No